This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Huntington?s disease is linked to the insertion of glutamine (Q) in the protein huntingtin, resulting in polyglutamine (polyQ) expansions that self-associate to form aggregates. The length of the expansion correlates with the onset of Huntington?s disease. While polyQ aggregation has been the subject of intense study, a correspondingly thorough understanding of individual polyQ chains is lacking. Atomic resolution structural information for polyQ chains in aqueous solution is still absent from the literature. We have discovered experimentally that polyQ chains exhibit unexpected extremely high mechanical stabilities and in a preliminary study we were able to sample a small number of polyQ chain conformations that were similarly resilient. We propose to generate sufficiently long runs on ANTON that will explain the existence of such mechanically resilient conformations, what their structures are, and how they aggregate. Mechanical resilience allows these disordered structures to survive for a sufficiently long time for them to aggregate and resist proteasomes. In the proposed research we will investigate the conformation space of different length polyQs and their aggregation using ANTON.